The chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease and asthma, are induced by a serial of cell inflammations in the body. The immune cells and the inflammatory cells are attracted and activated to induce inflammation at the damage or infected site when various cells (i.e. the white blood cell, the lymphocyte, the endothelial cell and epithelial cell) in the body are infected or damaged and release exceed intermediates. A cascade of the inflammations in the body is typically in association with the expressions of some inflammatory mediators, and thus it becomes a major trend to research and develop new drugs by controlling inflammation-related molecule such as nitrous oxide synthetase, reactive oxygen species (ROS).
Reactive oxygen species (ROS) is a molecule with high oxidizing ability, which is associated in mechanisms including inflammation, metabolic disorders and cellular aging. Generation of ROS may be induced by intracellular or extracellular substances. When it is overexpressed in the cells, ROS will attack DNA, protein and membrane lipid to cause the unrepairable damages, which results in cancer, aging and vascular diseases. Among the mechanisms resulting in ROS accumulation, controlling xanthine oxidase (XO) for developing the anti-XO drugs can be used to prevent or treat the diseases resulted from excess of ROS, so that it is an urgent need to develop the anti-XO drugs.
XO can transform hypoxanthine into xanthine, and then transform xanthine into uric acid. The clinical common anti-XO drug, such as allopurinol for treating gout and hyperuricemia, can cause side effect and may induce hepatitis, renal disease and allergy. Therefore, an anti-XO drug with less side effects is needed.
In view of the drawbacks of current techniques, researchers and inventors take 18β-glycyrrhetinic acid as the starting material to synthesize different derivatives of 18β-glycyrrhetinic acid by chemical reactions. After testing the biological activity, it is found that the derivatives of the present invention have inhibitory effects on inflammation and XO activity, and are valuable in developing an anti-inflammatory and anti-oxidant drug. Further, the synthesized active derivatives have a low cost and can be made in a mass production. Such chemical synthesis enables to modify the structure of the compounds for improving their activities and to estimate the yield of the compounds, which advantages the drug development. The summary of the present invention is described below.